Vascular Alterations in the Prediabetic Condition

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DESCRIPTION (provided by applicant): Cynthia Cheng MD, PhD is an instructor in Family Medicine. She holds a doctoral degree in Pharmacology. Dr. Cheng's career goal is to become an established investigator in cardiovascular disease research; specifically, she is interested in the early phase of vascular injury in diabetes and hypertension. Together with her mentor Dr. Falkner, Dr. Cheng has developed a concept derived from three well established observations: 1) The morbidity and mortality suffered by patients with diabetes are consequences of vascular disease; 2) Patients with high blood pressure (a disorder of the vasculature) have a greater risk for development of type 2 diabetes; and 3) Insulin resistance precedes type 2 diabetes and is common among patients with hypertension. Therefore, patients with high blood pressure and insulin resistance may have underlying vascular disease that precedes and contributes to the expression of diabetes. Accordingly, the overall hypothesis for this project is: Microvascular disease precedes the onset of clinical diabetes. Subjects with both high blood pressure and the prediabetic condition of insulin resistance plus impaired fasting glucose will have alterations in microvascular structure. The Research Specific Aims are to: 1. Develop a cohort of adults that includes a sample with high blood pressure (130-160 mmHg systolic) who also have insulin resistance, and a sample of age/race/sex matched adults with normal blood pressure (<130 mmHg systolic) and insulin sensitivity. 2. Measure small vessel structure in peripheral nail beds using capillaroscopy. 3. Measure vascular function by forearm blood flow and determine forearm vascular resistance at maximal vasodilation. 4. Determine if there are other markers of vessel injury in the cohort by assessing urinary albumin excretion. To conduct this research plan, Dr Cheng will work in Dr. Falkner's laboratory to master the established procedures on metabolic assessment and forearm blood flow, and Dr. Cheng will develop the methodology to examine microvascular structure by intravital capillary microscopy. Data generated in this project will be utilized to construct hypothesis driven research applications to continue Dr. Cheng's investigations in this area of clinical research. Data obtained from investigations of the early phase of vascular injury may reduce cardiovascular disease morbidity by contributing to improved strategies to identify, prevent and reverse the vascular pathology of diabetes and hypertension.